This invention pertains to a process for making L-gulono gamma lactone, also known as gulonic acid lactone or gulonolactone, from polyglucuronic acid or a lower alkyl glucuronoside.
It pertains particularly to a process for making L-gulono gamma lactone from either cellulose or starch as the ultimate starting material for the synthetic procedure.
L-gulono gamma lactone is a material of great present and potential interest since it can be converted chemically or biologically to L-ascorbic acid (vitamin C). Thus if a synthetic route were to be provided for the production of L-gulonic acid from cellulose or starch, a route also would be provided for the ultimate conversion of these low-cost materials to vitamin C. Furthermore, this route would include fewer and less expensive synthetic operations than does the classis Reichstein synthesis which presently is used universally in all commercial vitamin C manufacturing procedures.
It accordingly is the general purpose of the present invention to provide an efficient, practical, low-cost process for producing L-gulono gamma lactone in high yield from either polyglucuronic acid, an easily obtained cellulose or starch derivative, or from a lower alkyl glucuronoside such as methyl glucuronoside, which is easily obtained from methyl glucoside which, in turn, is easily obtained from starch.
The prior art contains references to synthetic procedures of possible interest in carrying out this conversion.
Sharkov in Angew. Chem. Internat. Edit. Volume 2, pages 405-409 (1963) discloses a process for converting polysaccharides to the corresponding polyhydric alcohols. Thus cellulose is converted to sorbitol by hydrogenation at 160.degree.-165.degree. C., 60-80 atm. hydrogen pressure and a reaction time of 50-60 minutes in aqueous acid medium using a ruthenium catalyst. However, the use of cellulose as a starting material under the reaction conditions specified leads to the production of a polyhydric alcohol product, sorbitol, rather than the L-gulono gamma lactone product which is the product of the process disclosed herein.
German Pat. No. 618907 (Hoffman-LaRoche; May 13, 1934) discloses another procedure of interest.
In accordance with this procedure, polyhydroxy carbonic acids are prepared from the corresponding uronic acids by hydrogenating the latter in aqueous acid, under pressure and at elevated temperatures which do not essentially exceed 140.degree. C. A nickel oxide-clay catalyst is specified. Specific procedures are given for converting mono-acetone-D-xyluronic to L-xylonic acid lactone and for converting alpha-D-methyl galacturoniside to L-galactonic acid. However, our attempts to apply the Hoffman-LaRoche procedure to the conversion of either polyglucuronic acid or methylglucuroniside to L-gulono gamma lactone resulted in failure because the nickel catalyst dissolved in the sulfuric acid reaction medium.
We now have discovered that L-gulono gamma lactone may be prepared easily and in high yields by the simple one-step procedure of simultaneously hydrolyzing and reducing polyglucuronic acid or an alkyl glucuroniside to the desired product.
The reduction is carried out with gaseous hydrogen in aqueous medium at a pH below about 4, at a reaction temperature of from about 100.degree. to about 140.degree. C., at a pressure of from about 600 to about 1500 psi in the presence of a periodic table Group VIII noble metal catalyst.
The reduction is carried out for a time sufficient to hydrolyze the glucosidic starting material to the corresponding free aldehyde (glucuronic acid) and to reduce the resulting free aldehyde to the desired L-gulono gamma lactone.
The possibility of obtaining successful results from this sequence is surprising, since the free aldehyde acide produced as an intermediate belongs to a class of compounds which de-carboxylate readily in acid solution. It therefore would be expected that it would lose carbon dioxide with resultant impossibility of subsequent conversion by reduction to L-gulono gamma lactone.
We have discovered, however, that under the reaction conditions stipulated herein, the starting materials are hydrolyzed slowly to the corresponding free aldehyde acid, i.e. to glucuronic acid. The latter, however, is reduced very rapidly to L-gulono gamma lactone. The reduction reaction accordingly takes place before the de-carboxylation occurs to any substantial extent. As a result, by the present method L-gulono gamma lactone may be obtained easily, economically and in many cases in yields in excess of 90% of the theoretical.
The reactions set forth herein are further unique in their selection of starting materials. Sharkov (supra) practices his described catalytic reduction in acid medium on cellulose as a starting material and obtains a polyhydric alcohol product. We employ either polyglucuronic acid, or an alkyl glucuronoside as starting materials. Our starting materials are characterized by the presence of a carboxyl group in their molecular structure. The complex cellulosic molecule is not characterized by the presence of free carboxyl groups.
In our synthetic procedure we have taken advantage of the fact that free carboxyl groups are not reduced under the catalytic hydrogenation conditions which we employ. Accordingly, we are enabled to produce the desired, commerically valuable, carboxyl-containing end product.